Abstract

Human meniscus cells have a predominantly fibrogenic pattern of gene expression, but
like chondrocytes they proliferate in monolayer culture and lose the expression of
type II collagen. We have investigated the potential of human meniscus cells, which
were expanded with or without fibroblast growth factor 2 (FGF2), to produce matrix
in three-dimensional cell aggregate cultures with a chondrogenic medium at low (5%)
and normal (20%) oxygen tension. The presence of FGF2 during the expansion of meniscus
cells enhanced the re-expression of type II collagen 200-fold in subsequent three-dimensional
cell aggregate cultures. This was increased further (400-fold) by culture in 5% oxygen.
Cell aggregates of FGF2-expanded meniscus cells accumulated more proteoglycan (total
glycosaminoglycan) over 14 days and deposited a collagen II-rich matrix. The gene
expression of matrix-associated proteoglycans (biglycan and fibromodulin) was also
increased by FGF2 and hypoxia. Meniscus cells after expansion in monolayer can therefore
respond to chondrogenic signals, and this is enhanced by FGF2 during expansion and
low oxygen tension during aggregate cultures.